S286: LONG-TERM EFFICACY AND SAFETY RESULTS FROM AN ONGOING OPEN-LABEL PHASE 2 STUDY OF PARSACLISIB FOR THE TREATMENT OF AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
Authors: W. Barcellini, I. Murakhovskaya, L. Terriou, F. Pane, A. Patriarca, K. Butler, S. Moran, S. Wei, U. Jäger
Journal: HemaSphere (2022)

Background: AIHA is a rare condition caused by autoantibody-mediated hemolysis of red blood cells. Few therapies beyond steroids and rituximab are available. Aims: To report updated results from an ongoing multicenter, phase 2, open-label study of the phosphoinositide 3-kinase-δ inhibitor parsaclisib in patients (pts) with AIHA (NCT03538041). Methods: Pts ≥18 years old with warm AIHA (wAIHA), cold agglutinin disease (CAD), or mixed-type AIHA; hemoglobin (Hgb) 7–10 g/dL; and failure of ≥1 standard therapy were eligible. After informed consent, pts were treated with oral parsaclisib for 12 wk at a starting dose of 1.0 mg once daily (QD; cohort 1) or 2.5 mg QD (cohort 2). Increases to 2.5 mg QD were allowed in cohort 1 after 6 wk if no clinical response was achieved and/or transfusion was required; reductions to 1.0 mg QD were permitted in cohort 2 for tolerability issues. Concomitant corticosteroids (≤20 mg/d prednisone) were allowed. After 12 wk of treatment, pts responding on parsaclisib could continue into an extension period. Primary endpoints were efficacy (proportion of pts with complete response [CR; Hgb ≥12 g/dL] or partial response [PR; Hgb 10–12 g/dL or ≥2 g/dL increase from baseline, inclusive of CRs] at any visit from Wk 6–12) and safety (treatment-emergent adverse events [TEAEs]). Results: As of Aug 5, 2021, 25 pts enrolled and received parsaclisib (cohort 1, n=10 [8 with dose increase]; cohort 2, n=15); 20 pts (80%) completed 12 wk of treatment. Sixteen (64%), 6 (24%), and 3 (12%) pts had wAIHA, CAD, and mixed AIHA, respectively. Mean (SD) age was 61.6 (17.0) years; 14 pts (56%) were female and 23 (92%) were White. Mean (SD) Hgb at baseline was 8.9 (0.8) g/dL, and 9 pts (36%) had transfusions in the past year. Mean parsaclisib exposure was 334 (range, 7–819) days. Overall, 8 pts (32%) achieved CR and 16 (64%) had PR at any visit from Wk 6–12. Among pts with wAIHA (n=16), 14 pts (88%) completed 12 wk of treatment; 8 (50%) and 12 (75%) achieved CR and PR, respectively, at any visit from Wk 6–12. Seventeen pts entered the extension period (12 with wAIHA). Increase in Hgb was sustained in the total cohort and among pts with wAIHA during the initial 12-wk treatment and extension periods (Figure). During the 12-wk treatment period, TEAEs occurred in 21 pts (84%) overall. Six pts (24%) had grade (Gr) ≥3 TEAEs, with only neutropenia occurring in >1 pt (n=2 [8%]); 2 pts (8%) had serious AEs (SAEs). Seven pts (28%) had treatment-related AEs, with only pruritic rash reported in >1 pt (n=2 [8%]). Three pts discontinued during the 12-wk treatment period (AE [n=1; thrombocytopenia], lack of efficacy [n=1], withdrawal by subject [n=1]), and 2 pts were of unknown status. During the extension period, 15/17 pts (88%) experienced ≥1 TEAE. Gr ≥3 AEs and SAEs were each reported in 9 pts (53%). Six pts (35%) had treatment-related AEs, with diarrhea and rash reported in >1 pt (n=2 [12%] each). One Gr 3 TEAE (psoriasis) and 3 SAEs (diarrhea [Gr 2], cytomegalovirus reactivation [Gr 2], psoriasis [Gr 3]) were deemed treatment related. Two (12%) pts had TEAEs leading to parsaclisib discontinuation. One fatal TEAE (acute respiratory failure in the extension period) was deemed unrelated to parsaclisib. Image:Summary/Conclusion: Parsaclisib was generally well tolerated and resulted in Hgb improvements as early as Wk 2 that increased over 12 wk of treatment and were sustained through the extension period. Parsaclisib may be an effective oral treatment for AIHA, and a randomized, controlled phase 3 trial in wAIHA is now recruiting (NCT05073458).